Previous studies in our laboratory have indicated that the humoral response to isografts of hamster cells transformed by PARA-(defective SV40) adenovirus 7 is quite complex. First, there is a factor(s) which can initiate the specific killing of tumor cells by non-sensitized lymphoid cells. Second, certain substances in tumor bearer sera can inhibit the cytotoxic activity of sensitized lymphocytes for the tumor cells. Third, after tumor excision a factor(s) is detectable that neutralizes the serum blocking effect. The humoral factors participating in antibody-dependent cellular cytotoxicity (ADCC), blocking, and unblocking have not yet been clearly defined, and what role, if any, they may play in affecting lymphocyte-tumor cell interaction in vivo is not known. Using microcytotoxicity assays, experiments will be directed toward a) identifying the humoral and cellular elements involved in each reaction, b) investigating the mechanism, and c) ascertaining the common and unique features of the three phenomena. Soluble tumor antigen, fractionated anti-tumor immunoglobulins, and immune complexes will be employed as appropriate in studies with normal or sensitized lymphoid cells. Studies will also be carried out to ascertain if the serum factors active in vitro can affect tumor growth in vivo. We will determine if passive transfer of serum blocking factors can facilitate PARA-7 tumor cell growth in normal or immunized syngeneic hosts. The relationship of the three phenomena to effective cyclophosphamide therapy will also be examined. Sera with ADCC or unblocking activity will be tested for their immunotherapeutic potential. These studies should contribute to our understanding of ADCC, blocking, and unblocking, and provide information as to what relevance these phenomena have to the neoplastic disease process.